The usefulness of an animal model for the study of anti-caries immunity is dependent upon the pathogenicity of the test bacterium, suseptibility of host animal to caries attack by this microorganism, the specificity of caries attack and the immune response to this bacterium. Gnotobiotic rats feed a defined diet containing 5% sucrose and infected with Streptococcus mutans serotypes and their hyperactive and avirulent mutans have been employed as a model for our studies. Using this system we have investigated effective methods for the induction of caries immunity and the immune mechanisms involved. Early studies indicated that local injection in the region of salivary glands resulted in a significant secretory immune response which afforded protection against subsequent caries attack. Later studies indicated that similar protective responses could be induced by ingestion of killed S. mutans. This response was probably due to stimulation of precursor secretory IgA lymphocytes in the gut associated lymphoid tissue which subsequently home to remote secretory tissues such as mammary and salivary glands. This hypothesis is supported by the fact that introduction of antigen by gastric intubation results in an equivalent response. In dose response studies we have shown that 10 to the minus 7th power to 10 to the minus 8th power bacterial colony-forming units per gm of diet represents an optimal antigen concentration; higher doses induce unresponsiveness in the secretory immune compartment. Additional work has shown that cross-immune protection can be effected by using GTF defective mutants (S. mutans 6715, C4) when challenged with hyperactive S. mutans (6715, C211). The cellular aspects and dynamics of the secretory response, including homing and subsequent antibody formation, and the potential for an anamnestic response are also being investigated. The role of innate immune factors, and their interaction with secretory antibodies are being studied both in vivo and in vitro.